The goal of this research is to improve our understanding of respiratory, metabolic and cardiovascular control during exercise and to elucidate the mechanisms by which diseases limit work performance. Computerized data analysis will be used to yield descriptions of dynamic physiological responses to exercise. While exercise is the principal cardio-respiratory stress, there is no consensus on the mechanism of the exercise hyperpnea. However, evidence is accumulating which suggests that exercise hyperpnea is closely coupled to CO2 delivery to the lung. This would imply that the chemical controller functions to keep arterial PCO2 relatively fixed by stimulating ventillation proportional to CO2 delivery to the lung. We propose to test this hypothesis during: 1) onset, 2) transition to steady-state, and 3) steady-state of exercise while perturbing certain physiological factors. We will study effects of limiting the rate of cardiac output increase, altering the CO2 set-point, attenuating the carotid bodies with 100% O2, varying O2 output by diet, and continuously varying dead space. Responses will be studied below and above the anaerobic threshold to discern the effects of superimposed metabolic acidosis. An additional thrust will be to study factors affecting gas exchange during exercise in health and disease. A single exercise test to measure anaerobic threshold, maximal O2 uptake, work efficiency and the time constant of O2 uptake kinetics has been developed and will be used to evaluate the alterations in gas exchange induced by various cardiovascular and respiratory disorders. The pathophysiological processes which alter breathing patterns will be studied in order to define the usefulness of these measurements in the differential diagnosis of patients limited in the performance of exercise.